Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic beta-cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non-autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1alpha. The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF-1alpha protein. Reporter gene analysis indicated that the mutant HNF-1alpha had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1alpha may lead to severe forms of diabetes like type 1 diabetes.
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PMID:Analysis of a non-functional HNF-1alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes. 1166 18

Maturity onset diabetes of the young (MODY) is characterized by a primary defect in insulin secretion and hyperglycemia, nonketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2-5% of all cases of non-type 1 diabetes. The diagnosis may be made by careful clinical evaluation, but exact subtyping is possible only by genetic analysis. Several genetic factors have been identified as causative agents in MODY, each leading to a different type of the disease. These include the enzyme glucokinase, which causes MODY2, and the transcription factors HNF- 4 alpha, TCF1, I PF-1, TCF2, and NeuroD1, which cause MODY1, 3, 4, 5, and 6, respectively. The genetic findings have important clinical implications, allowing for proper genetic counseling, early diagnosis, and better care of patients.
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PMID:Maturity onset diabetes of the young--review. 1755 75